Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted in the United States of America (USA). The aim of this clinical trial is to assess the implications of switching from insulin glargine (IGlar) to insulin degludec (IDeg) in subjects with type 2 diabetes mellitus.
Interventions
DRUGinsulin degludec
Individually adjusted insulin degludec administered three times weekly with continued unchanged pre-trial OAD (oral anti-diabetic drug) treatment for 12 weeks
DRUGinsulin glargine
Subjects continue their pre-trial insulin glargine once daily plus OAD (oral anti-diabetic drug) treatment for four weeks before switch to insulin degludec
Sponsors
Novo Nordisk A/S
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes mellitus (diagnosed clinically) for at least 6 months * HbA1c maximum 10 % by central laboratory analysis * Current treatment with basal-oral therapy (BOT) (no prandial insulin ever) consisting of: at least three months with insulin glargine once daily (average prescribed dose must have been unchanged (within plus/minus 10%) for four weeks prior to Visit 1 as confirmed by patient records or verbal confirmation by the subject) in combination with stable (unchanged doses for at least 3 months prior to Visit 1) OAD (metformin, insulin secretagogues, pioglitazone, sitagliptin or alpha-glucosidase-inhibitor) treatment in any approved (according to label) dose or combination
Exclusion criteria
* Use within the last three months prior to Visit 1 of: Exenatide, Liraglutide or Thiazoledinediones (TZDs) other than Pioglitazone * Cardiovascular disease (CVD) defined as: stroke; decompensated heart failure New York Heart Association (NYHA) class III or IV; myocardial infarction; unstable angina pectoris; or coronary arterial bypass graft or angioplasty within the last six months prior to Visit 1 * Recurrent severe hypoglycaemia (more than one severe hypoglycaemic episode during the last 12 months), or hypoglycaemic unawareness as judged by the Investigator, or hospitalisation for diabetic ketoacidosis during the previous six months * Pregnancy, breast-feeding, the intention of becoming pregnant or not using adequate contraceptive measures according to local requirements * Previous participation in this trial. Participation is defined as started on trial medication. Rescreening of screening failures is allowed only once within the limits of the recruitment period * Known or suspected hypersensitivity to trial products or related products
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HbA1c (Glycosylated Haemoglobin) | Week 4 and Week 16 | HbA1C at week 4 and 16 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fasting Plasma Glucose (FPG) | Week 4 and Week 16 | FPG at week 4 and 16 |
| Change in Body Weight | Week 0, Week 4, Week 16 | Change from baseline in body weight after week 4 and after week 16 |
| Rate of Treatment Emergent Adverse Events (AEs) | Weeks 0-4 (IGlar), Weeks 4-16 (IDeg 3TW) | Corresponds to rate of AEs per 100 patient years of exposure. Mild AEs: no or transient symptoms, no interference with subject's daily activities. Moderate AEs: marked symptoms, moderate interference with subject's daily activities. Severe AEs: considerable interference with subject's daily activities, unacceptable. Serious adverse event (SAE): AE that at any dose results in any of the following: death, a life-threatening experience, in-subject hospitalization/prolongation of existing hospitalisation, persistent/significant disability/incapacity/congenital anomaly/birth defect |
| Rate of Confirmed Hypoglycaemic Episodes | Weeks 0-4 (IGlar), Weeks 4-16 (IDeg 3TW) | Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes with a confirmed plasma glucose value of less than 3.1 mmol/L. |
| Rate of Nocturnal Confirmed Hypoglycaemic Episodes | Weeks 0-4 (IGlar), Weeks 4-16 (IDeg 3TW) | Rate of nocturnal confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes with a confirmed plasma glucose value of less than 3.1 mmol/L. Nocturnal hypoglycaemic episodes are defined as occuring between 00:01 and 05:59 a.m. |
Countries
United States
Participant flow
Recruitment details
The trial was conducted at 27 sites in the United States of America (U.S.)
Pre-assignment details
The trial was conducted on subjects with type 2 diabetes mellitus currently treated with IGlar once daily (OD) and oral antidiabetic drug (OAD) therapy.
Participants by arm
| Arm | Count |
|---|---|
| IGlar/IDeg Subjects received 4 weeks of unchanged pre-trial insulin glargine (IGlar) once daily (OD) followed by 12 weeks of insulin degludec (IDeg) 200 U/mL 3 times weekly (3TW) subcutaneously, both in combination with unchanged pre-trial oral antidiabetic drug \[OAD\] treatment. | 129 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Unclassified | 7 |
| Overall Study | Withdrawal criteria | 10 |
Baseline characteristics
| Characteristic | IGlar/IDeg |
|---|---|
| Age, Continuous | 58.7 years STANDARD_DEVIATION 10.2 |
| Body weight at baseline | 99.3 kg STANDARD_DEVIATION 20.4 |
| Fasting plasma glucose (FPG) at baseline | 7.0 mmol/L STANDARD_DEVIATION 2.2 |
| HbA1c (glycosylated haemoglobin) at baseline | 7.5 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1.1 |
| Sex: Female, Male Female | 43 Participants |
| Sex: Female, Male Male | 86 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 142 |
| serious Total, serious adverse events | 3 / 142 |
Outcome results
Primary
HbA1c (Glycosylated Haemoglobin)
HbA1C at week 4 and 16
Time frame: Week 4 and Week 16
Population: FAS (Full Analysis Set) includes all subjects that were switched to IDeg 3TW treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IGlar/IDeg | HbA1c (Glycosylated Haemoglobin) | Week 16 (N=122)(IDeg) | 7.2 percentage of glycosylated haemoglobin | Standard Deviation 1.1 |
| IGlar/IDeg | HbA1c (Glycosylated Haemoglobin) | Week 4 (N=128) (IGlar) | 7.4 percentage of glycosylated haemoglobin | Standard Deviation 1 |
Secondary
Change in Body Weight
Change from baseline in body weight after week 4 and after week 16
Time frame: Week 0, Week 4, Week 16
Population: Safety Analysis Set includes all subjects who received at least one dose of the investigational product or its comparator. Missing data is imputed using LOCF (last observation carried forward)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IGlar/IDeg | Change in Body Weight | Week 4(N= 142) (IGlar) | 0.1 kg | Standard Deviation 0.4 |
| IGlar/IDeg | Change in Body Weight | Week 16 (N=129) (IDeg) | 0.6 kg | Standard Deviation 2.2 |
Secondary
Fasting Plasma Glucose (FPG)
FPG at week 4 and 16
Time frame: Week 4 and Week 16
Population: FAS (Full Analysis Set) includes all subjects that were switched to IDeg 3TW treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IGlar/IDeg | Fasting Plasma Glucose (FPG) | Week 4 (N=128) (IGlar) | 7.0 mmol/L | Standard Deviation 2.3 |
| IGlar/IDeg | Fasting Plasma Glucose (FPG) | Week 16 (N=122) (IDeg) | 6.3 mmol/L | Standard Deviation 2.2 |
Secondary
Rate of Confirmed Hypoglycaemic Episodes
Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes with a confirmed plasma glucose value of less than 3.1 mmol/L.
Time frame: Weeks 0-4 (IGlar), Weeks 4-16 (IDeg 3TW)
Population: Safety Analysis Set includes all subjects who received at least one dose of the investigational product or its comparator.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IGlar/IDeg | Rate of Confirmed Hypoglycaemic Episodes | IGlar (N=142) (week 4) | 453 episodes per 100 patient years |
| IGlar/IDeg | Rate of Confirmed Hypoglycaemic Episodes | IDeg (N=129) (week 16) | 424 episodes per 100 patient years |
Secondary
Rate of Nocturnal Confirmed Hypoglycaemic Episodes
Rate of nocturnal confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes with a confirmed plasma glucose value of less than 3.1 mmol/L. Nocturnal hypoglycaemic episodes are defined as occuring between 00:01 and 05:59 a.m.
Time frame: Weeks 0-4 (IGlar), Weeks 4-16 (IDeg 3TW)
Population: Safety Analysis Set includes all subjects who received at least one dose of the investigational product or its comparator
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IGlar/IDeg | Rate of Nocturnal Confirmed Hypoglycaemic Episodes | IGlar (week 4) (N=142) | 111 episodes per 100 patient years |
| IGlar/IDeg | Rate of Nocturnal Confirmed Hypoglycaemic Episodes | IDeg (week 16) (N=129) | 83 episodes per 100 patient years |
Secondary
Rate of Treatment Emergent Adverse Events (AEs)
Corresponds to rate of AEs per 100 patient years of exposure. Mild AEs: no or transient symptoms, no interference with subject's daily activities. Moderate AEs: marked symptoms, moderate interference with subject's daily activities. Severe AEs: considerable interference with subject's daily activities, unacceptable. Serious adverse event (SAE): AE that at any dose results in any of the following: death, a life-threatening experience, in-subject hospitalization/prolongation of existing hospitalisation, persistent/significant disability/incapacity/congenital anomaly/birth defect
Time frame: Weeks 0-4 (IGlar), Weeks 4-16 (IDeg 3TW)
Population: Safety Analysis Set includes all subjects who received at least one dose of the investigational product or its comparator.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IGlar/IDeg | Rate of Treatment Emergent Adverse Events (AEs) | Severe AEs (N=142)(week 4) (IGlar) | 19 events per 100 patient years |
| IGlar/IDeg | Rate of Treatment Emergent Adverse Events (AEs) | Serious AEs (n=129) (week 16) (IDeg) | 7 events per 100 patient years |
| IGlar/IDeg | Rate of Treatment Emergent Adverse Events (AEs) | Adverse events (N=142)(week 4)(IGlar) | 370 events per 100 patient years |
| IGlar/IDeg | Rate of Treatment Emergent Adverse Events (AEs) | Serious AEs (N=142 ) (week 4)(IGlar) | 9 events per 100 patient years |
| IGlar/IDeg | Rate of Treatment Emergent Adverse Events (AEs) | Moderate AEs (N=142) (week 4)(IGlar) | 102 events per 100 patient years |
| IGlar/IDeg | Rate of Treatment Emergent Adverse Events (AEs) | Mild AEs (N=142)(week 4) (IGlar) | 250 events per 100 patient years |
| IGlar/IDeg | Rate of Treatment Emergent Adverse Events (AEs) | Fatal AEs (N=142) (week 4) (IGlar) | 0 events per 100 patient years |
| IGlar/IDeg | Rate of Treatment Emergent Adverse Events (AEs) | Adverse events (N=129) (week 16) (IDeg) | 424 events per 100 patient years |
| IGlar/IDeg | Rate of Treatment Emergent Adverse Events (AEs) | Severe AEs (N=129) (week 16) (IDeg) | 10 events per 100 patient years |
| IGlar/IDeg | Rate of Treatment Emergent Adverse Events (AEs) | Moderate AEs (N=129) (week 16) (IDeg) | 132 events per 100 patient years |
| IGlar/IDeg | Rate of Treatment Emergent Adverse Events (AEs) | Mild AEs (N=129) (week 16) (IDeg) | 280 events per 100 patient years |
| IGlar/IDeg | Rate of Treatment Emergent Adverse Events (AEs) | Fatal AEs (N=129) (week 16) (IDeg) | 0 events per 100 patient years |
| IGlar/IDeg | Rate of Treatment Emergent Adverse Events (AEs) | Adverse Events (N=142) (Total) | 409 events per 100 patient years |
| IGlar/IDeg | Rate of Treatment Emergent Adverse Events (AEs) | Serious AEs (N=142) (Total) | 8 events per 100 patient years |
| IGlar/IDeg | Rate of Treatment Emergent Adverse Events (AEs) | Severe AEs (N=142) (Total) | 13 events per 100 patient years |
| IGlar/IDeg | Rate of Treatment Emergent Adverse Events (AEs) | Moderate AEs (N=142) (Total) | 124 events per 100 patient years |
| IGlar/IDeg | Rate of Treatment Emergent Adverse Events (AEs) | Mild AEs (N=142) (Total) | 273 events per 100 patient years |
| IGlar/IDeg | Rate of Treatment Emergent Adverse Events (AEs) | Fatal AEs (N=142)(Total) | 0 events per 100 patient years |